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Impact of T-cell depletion on outcome of patients undergoing allogeneic hematopoietic cell transplantation for myelodysplastic syndrome

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Myelodysplastic syndromes (MDS) are clonal stem cell disorders usually characterized by cytopenia and dysplasia. MDS are usually diagnosed during the sixth decade and are associated with reduced life expectancy, mainly… Click to show full abstract

Myelodysplastic syndromes (MDS) are clonal stem cell disorders usually characterized by cytopenia and dysplasia. MDS are usually diagnosed during the sixth decade and are associated with reduced life expectancy, mainly related to transformation to acute leukemia, infections, or bleeding. Currently, the only potentially curative treatment for MDS is allogeneic hematopoietic stem cell transplantation (HSCT) [1–3]. However, HSCT is associated with significant morbidity and mortality mainly related to acute or chronic graft-vs.-host disease (aGvHD or cGvHD) [4, 5]. In the Geneva Stem Cell Transplant Center we use partial in vitro T-cell-depleted grafts usually for patients in complete remission at transplant to reduce GvHD incidence [6]. Indeed, partial T-cell depletion decreases the number of alloreactive donor T cells triggering GvHD. However, it is hypothesized that this strategy could increase relapse incidence (RI) and decrease overall survival (OS) due to the loss of the graft-vs.-leukemia effect mediated by donor lymphocytes. Impact of partial T-cell depletion was previously investigated in a cohort of patients, including heterogeneous diseases and results had shown no worsening of outcome for partially T-cell-depleted patients [7]. However, the impact of partial T-cell depletion was never specifically investigated for patients undergoing transplantation for MDS. In this retrospective study, we investigated patients allografted for a diagnosis of MDS over a 19 years’ period (from 01 January 1998 to 31 August 2016). Patients aged ≥18 years old at transplant time, who had a diagnosis of MDS according to the 2008 World Health Organization criteria, and who had a first HSCT were included. Patients with haploidentical transplantation, stem cell from identical twins, umbilical cord blood transplantation, or more than two human leukocyte antigen (HLA) locior allelemismatched unrelated donor (MMUD) transplantation were excluded. This study was approved by an ethics committee. Primary outcomes were comparison of 3-year OS, progression-free survival (PFS), GvHD-free/relapse-free survival (GRFS) [8], RI, and non-relapse mortality (NRM) between partially T-cell-depleted patients and non-T-celldepleted ones. Secondary outcomes were impact of partial T-cell depletion on grade 2–4 acute and chronic GvHD. Sixty-two patients were included. Forty-four percent were female, median age at transplant was 48 years (range: 18–70 years) with myeloablative conditioning for 66% and reduced intensity for 34%. Median time from diagnosis to HSCT was 7.5 months (range: 3–86 months). Peripheral blood stem cell (90%) or bone marrow (BM; 10%) grafts were from HLA-identical siblings (45%), HLA-matched unrelated donor (MUD; 42%), or MMUD (13%). Antithymocyte globulin was used for 56% of patients and partial T-cell depletion was performed for 52% of patients. Median follow-up was 4.6 years (range: 0–15). Patients’ characteristics and data on transplantation are shown in Table 1. Myeloablative conditioning usually consisted of cyclophosphamide (120 mg/kg) with either total body irradiation These authors contributed equally: Maude Raboud, Yan Beauverd.

Keywords: cell depletion; stem cell; transplantation; partial cell; cell

Journal Title: Bone Marrow Transplantation
Year Published: 2018

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